buprenorphine and Spinal-Cord-Injuries

Our recent study revealed that spinal electromagnetic stimulation (sEMS) applied at low (0.2 Hz) frequencies may improve diminished transmission in damaged spinal cord in spinal cord injured (SCI) rats. We have recently begun a pilot study investigating the effects of sEMS in non-injured and SCI humans. One unexpected result was the reduction of chronic low back pain (CLBP), reported by some patients following sEMS treatment. Chronic low back pain is one of the main causes of disability affecting the general population. Opioids are the most common drugs prescribed to US adults with CLBP. To optimize parameters for sEMS for pain treatment, in this study we used the SCI animal model and examined effects of sEMS applied at lumbosacral level on parameters and frequency-dependent depression (FDD) of Hoffmann H-reflex responses, known as common neurophysiological measures for evaluation of sensorimotor condition and plasticity in humans. We have also examined the interactive effects of sEMS and the opiate partial agonist Buprenorphine on the parameters of H-reflex in naïve and SCI rats. Consistent with previous reports, chronic SCI resulted in a marked decrease of threshold intensity required to evoke H-reflex and a lesser rate of FDD of the H-response in adult rats. Our current study revealed the optimum parameters of spinal EMS for best recovery of the properties of the H-reflex in chronic SCI animals. Here we demonstrate that electro-magnetic stimulation applied at spinal L4-L5 level with a pulsed mode (pulse at 20 Hz frequency for 5 sec with 25 sec break between pulses, total 40 trains for 20 min; PSEMS) reversed effects of SCI on key parameters of H-reflex: i.e. (1) restored the threshold intensity of electric current applied at tibial nerve to evoke the H-reflex and (2) recovered FDD properties of the H-reflex in SCI rats. Importantly, subcutaneous injections of Buprenorphine, prior to PSEMS administration, abolished the ability of PSEMS to recover both threshold intensity and FDD of the H-reflex in chronic SCI animals. These results suggest that a semi-synthetic opioid Buprenorphine and PSEMS might share common sites of action. We thus conclude that PSEMS might carry potential as a non-invasive treatment approach for chronic low back pain.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Electromagnetic Phenomena; H-Reflex; Humans; Pilot Projects; Rats; Spinal Cord Injuries

The principles of Refinement, Replacement and Reduction (3R's) should be taken into account when animals must be used for scientific purpose. Here, a Reduction / Refinement approach was applied to the procedure of spinal cord injury (SCI), an animal model used in rehabilitation medicine research, in order to improve the quality of experiments, avoiding unnecessary suffering. The aims of this investigation were 1- to assess acute surgical pain in mice subjected to SCI, 2- to compare the efficacy of commonly used analgesia (three buprenorphine subcutaneous injection in 48 hours, 0,15 mg/kg each) with a combination of opioid and NSAID (one subcutaneous injection of 5 mg/kg carprofen before surgery followed by three buprenorphine subcutaneous injection in 48 hours, 0,15 mg/kg each) and 3- to test if Infrared Thermography (IRT) could be a potential new Refinement method to easily assess thermoregulation, an important metabolic parameter. Finally, we aimed to achieve these goals without recruiting animals on purpose, but using mice already scheduled for studies on SCI. By using behaviours analysis, we found that, despite being commonly used, buprenorphine does not completely relieve acute surgical pain, whereas the combination of buprenorphine and carprofen significantly decreases pain signs by 80%. IRT technology turned out to be a very useful Refinement tool being a non invasive methods to measure animal temperature, particularly useful when rectal probe cannot be used, as in the case of SCI. We could find that temperatures constantly and significantly increased until 7 days after surgery and then slowly decreased and, finally, we could observe that in the buprenorphine and carprofen treated group, temperatures were statistically lower than in the buprenorphine-alone treated mice. To our knowledge this is the first work providing an analgesic Refinement and a description of thermoregulatory response using the IRT technology, in mice subjected to SCI.

Topics: Analgesics; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Carbazoles; Disease Models, Animal; Infrared Rays; Male; Mice; Mice, Inbred C57BL; Pain Measurement; Pain, Postoperative; Rehabilitation Research; Spinal Cord Injuries; Thermography

An online questionnaire.. To assess the international spinal cord medicine and rehabilitation community's utilization of pharmacological and non-pharmacological treatments for spinal cord damage (SCD)-related pain and to determine whether approaches to SCD-related pain differ between developed and less developed nations.. An international collaboration of authors.. An on-line survey querying availability and utilization of a number of approaches to SCD-related pain was developed, distributed, and made available for 6 months. Responses were analyzed for the entire cohort and according to participants' descriptions of their home nations' economies.. Most spinal cord medicine clinicians employ a multimodal approach to pain. There are significant differences in utilization of pharmacologic and non-pharmacologic approach to SCD-related pain between clinicians from more and less developed countries.

Topics: Acupuncture Therapy; Analgesics, Opioid; Buprenorphine; Cognitive Behavioral Therapy; Developed Countries; Developing Countries; Humans; Implantable Neurostimulators; Medical Marijuana; Mindfulness; Nurse Practitioners; Pain Management; Physical Therapists; Physician Assistants; Physicians; Practice Patterns, Physicians'; Spinal Cord Injuries; Surveys and Questionnaires

A limitation of animal models of central pain is their inability to recapitulate all clinical characteristics of the human condition. Specifically, many animal models rely on reflexive measures of hypersensitivity and ignore, or cannot assess, spontaneous pain, the hallmark characteristic of central pain in humans. Here, we adopt a conditioned place preference paradigm to test if animals with lesions in the anterolateral quadrant of the spinal cord develop signs consistent with spontaneous pain. This paradigm relies on the fact that pain relief is rewarding to animals, and has been used previously to show that animals with peripheral nerve injury develop tonic pain. With the use of 2 analgesic treatments commonly used to treat patients with central pain (clonidine infusion and motor cortex stimulation), we demonstrate that analgesic treatments are rewarding to animals with spinal cord lesions but not sham-operated controls. These findings are consistent with the conclusion that animals with spinal cord injury suffer from tonic pain.. The hallmark characteristic of central pain in humans is spontaneous pain. Animal models of central pain rely on reflexive measures of hypersensitivity and do not assess spontaneous pain. Demonstrating that animals with spinal cord injury suffer from tonic pain is important to study the etiology of central pain.

Topics: Analgesics; Animals; Buprenorphine; Clonidine; Conditioning, Operant; Disease Models, Animal; Electric Stimulation; Female; Hyperalgesia; Motor Cortex; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Spinal Cord Injuries

Acute pain is a common symptom experienced after spinal cord injury (SCI). The presence of this pain calls for treatment with analgesics, such as buprenorphine. However, there are concerns that the drug may exert other effects besides alleviation of pain. Among those reported are in vitro changes in gene expression, apoptosis, and necrosis. In this investigation, the effect of buprenorphine was assessed at the molecular, behavioral, electrophysiological, and histological levels after SCI. Rats were injured at the T10 thoracic level using the NYU impactor device. Half of the animals received buprenorphine (0.05 mg/kg) for 3 consecutive days immediately after SCI, and the other half were untreated. Microarray analysis (n = 5) was performed and analyzed using the Array Assist software. The genes under study were grouped in four categories according to function: regeneration, apoptosis, second messengers, and nociceptive related genes. Microarray analysis demonstrated no significant difference in gene expression between rats treated with buprenorphine and the control group at 2 and 4 days post-injury (DPI). Experiments performed to determine the effect of buprenorphine at the electrophysiological (tcMMEP), behavioral (BBB, grid walking and beam crossing), and histological (luxol staining) levels revealed no significant difference at 7 and 14 DPI in the return of nerve conduction, functional recovery, or white matter sparing between control and experimental groups (p > 0.05, n = 6). These results show that buprenorphine (0.05 mg/kg) can be used as part of the postoperative care to reduce pain after SCI without affecting behavioral, physiological, or anatomical parameters.

Topics: Analgesics, Opioid; Animals; Apoptosis; Buprenorphine; Disease Models, Animal; Evoked Potentials, Motor; Female; Gait Disorders, Neurologic; Gene Expression Regulation; Locomotion; Nerve Regeneration; Nerve Tissue Proteins; Neural Conduction; Nociceptors; Oligonucleotide Array Sequence Analysis; Pain, Intractable; Rats; Rats, Sprague-Dawley; Recovery of Function; Second Messenger Systems; Spinal Cord Injuries; Treatment Outcome

We have studied and compared the antinociceptive and anti-hyperalgesic effect of the partial opioid receptor agonist buprenorphine in normal and neuropathic rats. In normal rats, systemic buprenorphine produced dose-dependent antinociception on the hot plate test. In rats with peripheral nerve or spinal cord injury, buprenorphine markedly alleviated neuropathic pain-related behaviors, including mechanical and cold allodynia/hyperalgesia at doses comparable to that producing antinociception. The results suggest that buprenorphine may be a useful analgesic for treating neuropathic pain and thus is an atypical opioid since morphine tends to be less potent after nerve injury.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Dose-Response Relationship, Drug; Female; Injections, Spinal; Injections, Subcutaneous; Male; Pain; Pain Measurement; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Spinal Cord Injuries; Time Factors